Multiple myeloma (MM) is a cancer of bone marrow plasma cells that results in over ten thousand deaths a year in the USA.It is always preceded by a pre-malignant phase called monoclonal gammopathy of undetermined significance (MGUS). MGUS is very common (4% of adults), and overall has a low risk (~1-2%) each year of progressing to MM. We are unable to prevent the progression to MM, and currently recommend that patients with MGUS be followed annually. Unfortunately most patients progress to MM between the annual visits, sufferring from the complications of MM that include bony disease, anemia, and renal insufficiency. Most of the genetic changes identified in MM are also present in MGUS, however recently we have identified candidate genetic mutations that may drive the progression of MGUS to MM, potentially providing a useful genetic biomarker. This project will explore the genetic differences between patients with MGUS and MM with the goal of understanding the genetic mechanisms of progression and improving our risk prediction models, and preventing MGUS patients from suffering the complications of MM.